穿心莲内酯制剂及药代动力学的研究进展

穿心莲内酯是一种具有半日花烷骨架的天然二萜内酯类化合物,对诸多感染性疾病均显示有突出的疗效,被誉为天然抗生素药物。然而,极低的生物利用度和不良口感使其直接应用于临床受到限制。近年来,通过各种新型制剂学手段改善其生物利用度和口感逐渐成为研究热点。与此同时,相应的药代动力学研究也日益受到关注。该文阐述了穿心莲内酯的剂型和药代动力学研究进展,以利为这一活性天然产物的深入开发应用提供依据。     

丹参及其制剂的体内药代动力学研究概述

丹参为唇形科鼠尾草属植物丹参的干燥根。传统医学认为 ,丹参归心、肝经 ,药性微寒 ,味苦、无毒 ,具有活血化瘀、清热解毒、除烦、镇痛、通经、镇静安神、凉血消肿之功效 ;现代医学认为 ,丹参具有扩张冠状动脉 ,增加冠脉血流量 ,防止心肌缺血和心肌梗塞 ,加快微循环血流 ,促进毛细血管网开放 ,抑制心肌收缩 ,减少能量消耗 ,扩张血管 ,降低胆固醇、血脂 ,抑制凝血 ,激活纤溶 ,稳定红细胞膜 ,提高缺氧耐受力 ,增加肝脏血流量 ,保护肝损伤细胞 ,抗肝纤维化 ,抑制中枢神经系统 ,以及消炎抗菌等作用[1]。丹参中含有的成分可分为水溶性和脂溶性两…     

复方丹参方中使药冰片对君药丹参药代动力学的影响

目的:探讨复方丹参方中使药冰片对君药丹参药代动力学的影响.方法:选择家兔54只,按照随机数字表法分组,各27只.对照组以10g/kg丹参灌胃给药,研究组在对照组基础上配以0.18g/kg冰片灌胃给药.对比两组丹参素质量浓度与药代动力学相关参数.结果:研究组(10、30、60、90)min时丹参素质量浓度低于对照组,差异有统计学意义(P<0.05),(120、300)min时两组丹参素质量浓度差异无统计学意义(P>0.05);研究组t1/2α、t1/2β、CL/F、AUC、Ka及Tlag均优于对照组,差异有统计学意义(P<0.05),两组Cmax、Tmax差异无统计学意义(P>0.05).结论:复方丹参方中使药冰片有利于提高丹参分布率、吸收率及生物利用度,可有效增强药物治疗效果.     

尿中丹参素的测定及其在人体的药代动力学

目的：分析丹参素在人体内的药代动力学及其测定方法。方法采用尿药法研究丹参素的测定及其在人体的药代动力学。本文选取C18小柱对尿样中的丹参素进行净化和富集,然后再采用ODS柱上以乙腈－0．01mol? L －1磷酸二氢钾溶液（pH为2．8）为流动相,再进行280nm检测。结果健康人体po含丹参素20mg的复方中药颗粒剂B和丹参水煎剂后,丹参素的消除半衰期分别为（0．93±0．16）h、（0．94±0．24）h,8h内体积丹参素尿药累计排泄率分别为（6．21±2．79）％、（14．01±4．02）％。结论正常剂量下的丹参素可以由胃肠道直接吸收,并且可以经过原型从肾脏排泄。但是服用复方制剂后,丹参素的尿药累计排泄率与单用丹参煎剂对比显著降低,但两者的消除半衰期差异无统计学意义（P＞0．05）。     

尿中丹参素的测定及其在人体的药代动力学

目的研究丹参素在人体内的药代动力学。方法用尿药法研究丹参素的人体药代动力学。使用C₁₈小柱对尿样中的丹参素进行净化和富集，再在ODS柱上，以乙腈-0.01 mol·L^-1磷酸二氢钾溶液（pH 2.8）为流动相，在280 nm检测。结果健康志愿者po含丹参素20 mg的复方中药颗粒剂A和丹参水煎剂后，丹参素的消除半衰期t_1/2分别为(0.92±0.16) h和(0.94±0.21) h，8 h内丹参素尿药累积排泄率分别为(6.2±2.8)%和(14±4)%。结论 在正常剂量下，丹参素可由胃肠道吸收入人体，并可以原型从肾脏排泄；服用复方制剂后，丹参素的尿药累积排泄率较单用丹参煎剂显著降低，而二者的消除半衰期无显著差异。     

复方丹参滴丸与复方丹参片的药代动力学效果比较

目的 撂讨复方丹参制剂使用效果及其药代动力学。方法 分别采用尿样法和血浆萃取、色谱分析的方式束测量并分析对比复方丹参漓丸和复方丹参素的药动学参数。结果 丹参酮消除半衰期为0．55h,丹参素消除半衰期为0.92h。结论 复方丹参片药效发挥缓慢,不能用于缓解心绞痛;复方丹参漓丸可作为缓解心绞痛的急救药。     

眼表应用制剂进行人体药代动力学研究的意义与可行性

药代动力学研究在药品研发及评价过程中具有重要作用。本文对眼表应用制剂的药代动力学研究的意义及可行性进行了探讨。为国内该类药物的研发提供参考。     

紫杉醇药代动力学研究进展

通过检索近年来有关紫杉醇药代动力学研究文献,综述紫杉醇在药代动力学方面的研究进展,结果显示紫杉醇的代谢具有非线性药代动力学特征,闯与了这个过程,因此机体代谢功能差异不同避免地导致疗效和毒副作用的差异。     

大鼠静脉注射丹参酚酸B后的药代动力学研究

目的:建立丹参酚酸B的反相高效液相色谱分析方法,并对其在大鼠体内的药代动力学行为特性进行全面的分析研究。方法:生物样品采用液-液萃取方法,以Hypersil C18ODS色谱柱(200 mm×4 .6 mm,5μm) ,柱温40 ℃,流动相:乙腈水=20 80(含0 .25 mol/L乙酸胺) ,用磷酸调pH至4 .0 ,流速:1 .0 mL/min;紫外检测波长:328 nm。结果:鼠尾静脉给予丹参酚酸B1 .6、3 .2、6 .4 mg/kg后,结果显示鼠α相半衰期为(3 .1±0 .1) min,β相半衰期为(31 .5±3 .2) min。大鼠尾静脉给予丹酚酸B后,组织中浓度依次为(高→低) :心、肝、肺、小肠、肾脏、脾、胃、卵巢和脑组织。丹参酚酸B在粪便和尿中24 h及胆汁中2 h的累积排泄百分数分别约为1.43 %、0.77 %及8 .03%。丹参酚酸B人血浆蛋白结合率和大鼠血浆蛋白结合率分别为89 .2 %±1 .8 %和92 .5 %±1 .5 %。结论:本法准确、稳定、灵敏度高,适合生物样品中丹参酚酸B的分析。丹参酚酸B在大鼠体内消除速度快,血浆蛋白结合率较高,胆汁为其主要排泄途径。     

不同厂家复方丹参片水溶性成分含量的比较与分析

OBJECTIVETo determine the water-soluble effective components in compound Danshen tablets on market. METHODAdopted HPLC method to analyze the Danshensu and protocatechuicaldehyde(PCAD) in the ten batches of the tablets produced by seven manufactures. RESU     

effect of atorvastatin on the pharmacokinetics of diltiazem and its main metabolite,desacetyldiltiazem, in rats

The purpose of this study was to investigate the effect of atorvastatin, HMG-CoA reductase inhibitor, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 mg x kg(-1)) to rats pretreated with atorvastatin (0.5 or 2.0 mg x kg(-1)). Compared with the control (given diltiazem alone), the pretreatment of atorvastatin significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration (Cmax) and the areas under the plasma concentration-time curve (AUC) of diltiazem were significantly (p < 0.05, 0.5 mg x kg(-1); p < 0.01, 2.0 mg x kg(-1)) increased in the presence of atorvastatin. The AUC of diltiazem was increased by 1.40-fold in rats pretreated with 0.5 mg x kg(-1) atorvastatin, and 1.77-fold in rats pretreated with 2.0 mg x kg(-1) atorvastatin. Consequently, absolute bioavailability values of diltiazem pretreated with atorvastatin (8.4-10.6%)were significantly higher (p < 0.05) than that in the control group (6.6%). Although the pretreatment of atorvastatin significantly (p < 0.05) increased the AUC of desacetyldiltiazem, metabolite-parent AUC ratio (M.R.) in the presence of atorvastatin (0.5 or 2.0 mg x kg(-1)) was significantly decreased compared to the control group, implying that atorvastatin could be effective to inhibit the metabolism of diltiazem. In conclusion, the concomitant use of atorvastatin significantly enhanced the oral exposure of diltiazem in rats.     

HPLC法检查氯雷他定及其制剂的有关物质

目的:采用HPLC法检查氯雷他定及其制剂(片剂、胶囊、颗粒剂)的有关物质。方法:采用Diamonsil C_(18)(5μm,200mm×4.6mm)色谱柱,流动相:乙腈-0.05moL.L~(-1)磷酸二氢铵(用磷酸调pH为2.5)(50:50),检测波长245nm,柱温:40℃,流速:1.0mL.min~(-1) 。结果:在0.125mg·mL~1～1.25mg·mL~(-1)浓度范围内呈良好的线性关系,回归方程Y=1751C+50,相关系数r=0.99998,最低检测浓度80μg.mL~(-1),最低检测量1.6ng。结论:方法简便,快速,准确;可同时分离和测定氯雷定原料及其制剂的有关物质。     

The influence of cimetidine on the pharmacokinetics of diltiazem and its main metabolite in rabbits

The purpose of this study was to investigate the pharmacokinetic alteration of diltiazem and its main metabolite, deacetyldiltiazem, after oral administration of diltiazem in rabbits with or without cimetidine co-administration. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly elevated in rabbits pretreated with cimetidine, suggesting that the oral clearance, an index of intrinsic clearance, may be decreased by the cimetidine treatment. Consistent with the increased AUC by the treatment, peak plasma concentration (Cmax) for diltiazem was also elevated. Apparent volume of distribution normalized by the bioavailability (Vd/F) of diltiazem increased significantly in rabbits pretreated with cimetidine increased. Taken together with the fact that the first pass metabolism for diltiazem is the primary determinant for the oral bioavailability, these observations indicate that increases in the oral clearance and Vd/F may be a manifestation of the decreased first pass metabolism. Consistent with the hypothesis, the AUC of deacetyldiltiazem was significantly decreased in rabbits with cimetidine treatment. Ratio of deacetyldiltiazem to total diltiazem in the plasma was significantly decreased in rabbits with cimetidine treatment. These observations suggested that the metabolism of diltiazem to deacetyldiltiazem was reduced by cimetidine treatment and that the dosage of diltiazem should be adjusted when the drug is co-administered chronically with cimetidine in a clinical setting.     

Salicylamide pharmacokinetics in healthy males: Dietary effect

The effect of diet on the absorption, metabolism, and elimination of salicylamide (SAM) in man was studied in five healthy male volunteers. In a three-way cross-over study, 300 mg SAM capsules were administered under fasting, carbohydrate, and lipid diet conditions. Total urinary salicylates, salicylamide glucuronide (SAMG), and salicylamide sulphate (SAMS) were determined at different time intervals. Diet was found to have no significant effect on the extent of SAM absorption or on its apparent elimination half-life. A significant increase (P< 0.001) in the fraction excreted as SAMS in the lipid diet trial compared to the fasting or carbohydrate trials is observed. In the lipid diet trial, the ratio (R) of the cumulative urinary SAMS/SAMG was found to be 1.5–3 times the ratio obtained under fasting or carbohydrate diet conditions. The equilibrium solubilities of SAM under physiologic conditions in water (W), simulated intestinal fluid (M), and corn oil (O) were 4.08, and 4.81, and 12.5mgml^?1, respectively. The equilibrium apparent distribution coefficients K_O/W'K_O/W, and K_M/W were 3.1, 2.6, and 1.18, respectively. The increase in R is probably due to a decrease in free SAM concentration at the absorption site (intestinal mucosa) in the presence of lipids. A model for drug distribution in the gastrointestinal tract during lipid digestion is proposed and discussed.     

高效液相-荧光法测定人血浆中非布司他的浓度及其人体药动学研究

目的:建立测定人血浆中非布司他浓度的方法,研究非布司他片的药代动力学。方法:12名健康受试者采用3×3简化拉丁方设计,分别于不同周期服用40、80、120mg非布司他片进行单剂量药动学研究,按80mg剂量连续给药7d(每天一次)进行多剂量药动学研究。血样经含10%乙酸的乙腈萃取,采用高效液相-荧光法(HPLC-FLU)检测。以甲醇∶0.1%甲酸水溶液(71∶29,V/V,梯度:0～5.2min=71∶29,7～10min=90∶10,10.2～12.5min=71∶29)为流动相,流速:1mL/min。荧光检测器激发波长320nm,发射波长380nm。内标为2-萘甲酸。结果:该法在0.025～10mg/L浓度范围内呈线性关系,r=0.9996。最低检测浓度0.005mg/L,平均提取回收率为94.3%,日内RSD 1.53%、日间RSD2.27%。12名健康受试者单剂量口服非布司他40、80、120mg的主要药动学参数为Cmax=(1.63±0.54)、(3.59±1.23)、(4.76±1.15)mg/L,tmax=(1.29±0.60)、(1.06±0.68)、(1.71±0.98)h,AUClast=(4.94±1.21)、(11.68±2.80)、(18.93±5.27)mg.h.L-1;多剂量口服非布司他80mg Cmax=(4.19±1.44)mg/L,tmax=(1.31±0.97)h,AUCss=(12.42±3.31)mg.h.L-1。结论:口服非布司他片在健康人体内的药动学符合一级线性药代动力学特征,多次给药体内无蓄积作用。非布司他片在中国健康人体内的药动学行为与国外文献报道基本一致。     

头孢呋辛临床药动学的研究进展(英文)

目的综述头孢呋辛钠和头孢呋辛酯的临床药动学的研究进展。方法查阅国内外文献并进行分析归纳和总结。结果头孢呋辛在组织和体液中分布广泛,消除快,体内药动学行为符合二室开放模型,头孢呋辛酯水解后以头孢呋辛的形式起作用,饮食影响头孢呋辛酯的生物利用度,在特殊人群中用药量需酌情减量,未见性别差异。结论作为二代头孢类药物代表的头孢呋辛,已入选国家基本药物目录,但仍然需要检测患者血药浓度,避免抗生素滥用,实现个体化给药,达到临床的安全、合理、有效用药。     

松果菊苷药动/药效研究进展与思考

本文综述了近年来松果菊苷（ECH）在抗衰老、提高记忆力与神经保护、抗肿瘤、保护肝脏及免疫调节等方面的药理作用研究进展,探讨了其可能的作用机制。此外,还对ECH的吸收和代谢等药代动力学最新研究进展进行总结,并将其药效学特征与药代动力学行为进行联系与比较,指出了ECH药效学和药代动力学之间存在的表面矛盾,并就如何解释这些矛盾进行了探讨。在此基础上,提出天然来源的创新药物通常具有系统前广泛代谢的特点,发挥整体药效作用的可能是其活性代谢产物;应针对中药I类新药的这些特点,加强系统前代谢转化研究;并制订科学合理的临床前药物代谢动力学技术指导原则,用以指导具有类似特点的中药I类新药的研究。     

药理效应法测定参附注射液药动学参数的研究

目的:考察参附注射液在大鼠体内的药动学特征.方法:采用结扎冠状动脉法复制大鼠心源性休克模型,以血压值作为效应指标,选取1.25、2.5、5、10、20、25 mL/kg六个剂量参附注射液做量-效曲线,选择20 mL/kg剂量做时-效曲线,依据时-效曲线和量效曲线求得时间-生物体存量曲线,用DASver 2.0软件分析参附注射液的药动学参数.结果:主要药物动力学参数为t1/2=8.685 min,Ke=0.08 min-1, CL=1.417 L· min -1·kg-1, AUC(0-t) =12.63 mg·L-1·min-1.结论:在大鼠体内静脉注射参附注射液的体存量的表观动力学过程符合一室模型.     

壳聚糖在药物制剂中的应用研究进展

综述壳聚糖在生物大分子口服给药、pH敏感释药、靶向给药、纳米药物载体等药物制剂方面的应用研究进展。